Insomnia, often blamed on stress or bad sleep habits, may instead be closely linked to depression, heart disease, and other physiological disorders, a pair of deep dives into the human genome now reveals.

Michael Price, Science Mag, Feb 25, 2019

“Both studies are very well done,” says psychologist Philip Gehrman of the University of Pennsylvania’s Perelman School of Medicine, who researches sleep behavior. Still, he stresses that much more work remains before the genetic connections to insomnia can be translated to new therapies for patients.

Insomnia costs the U.S. workforce more than $63 billion each year in lost productivity, according to some estimates. It’s also incredibly common: As much as a third of the worldwide population suffers from insomnia-related symptoms at any given time. Yet the disorder remains poorly understood.

In one new paper reported today in Nature Genetics, researchers led by geneticist Danielle Posthuma of Vrije Universiteit in Amsterdam conducted a genome-wide association study (GWAS), which looks for links between shared sequences of DNA and particular behaviors or clinical symptoms. The group analyzed the genomes of more than 1 million people, which the authors say is the largest GWAS to date. The data came from UK Biobank, a long-running, enormous U.K. genetics study, and the private genetics firm 23andMe. The prevalence of insomnia in the people covered by both databases was about 30%, which is in line with estimates for the general population.

The scientists ultimately turned up 956 genes that predicted some level of insomnia risk. Many have been previously associated with depression, neuroticism, diabetes, and cardiovascular disease, yet they are only weakly linked to other sleep characteristics, such as quality of sleep and being a morning or night person. The team also found a link between insomnia and MEIS1, a gene previously tied to restless leg syndrome.

In another study appearing today in Nature Genetics, a different team also ran a GWAS on insomnia. The researchers, led by geneticist Richa Saxena of Massachusetts General Hospital in Boston, looked at 453,379 genomes. They found 57 chromosomal locations containing approximately 236 genes that are associated with insomnia symptoms. MEIS1 was one of them as well, and again there appeared to be a link between insomnia and genes involved with depression, coronary artery disease, and poorer self-reported quality of life. What’s more, the team’s analysis suggests insomnia can cause symptoms of depression and heart disease in some people.

“Insomnia is an important sleep disorder to be taken seriously, both for its impact on quality of life … and on future depression and heart disease,” Saxena says.

Identifying these genetic targets could allow researchers to more effectively tailor medicines and therapies, Posthuma says. For example, drugmakers could hunt for molecules that tamp down the activity of some of these genes. Alternatively, existing treatments for depression, such as antidepressants or cognitive behavioral therapy, might also help ease insomnia symptoms, Posthuma says.

Pinpointing the right targets out of the hundreds of gene candidates suggested by these studies will be the next difficult step, Gehrman says. Scientists, he notes, need “to figure out which ones are ‘real’ or just random associations.”